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dc.contributor.authorEscala-Garcia, M
dc.contributor.authorGuo, Q
dc.contributor.authorDörk, T
dc.contributor.authorCanisius, S
dc.contributor.authorKeeman, R
dc.contributor.authorDennis, J
dc.contributor.authorBeesley, J
dc.contributor.authorLecarpentier, J
dc.contributor.authorBolla, MK
dc.contributor.authorWang, Q
dc.contributor.authorAbraham, J
dc.contributor.authorAndrulis, IL
dc.contributor.authorAnton-Culver, H
dc.contributor.authorArndt, V
dc.contributor.authorAuer, PL
dc.contributor.authorBeckmann, MW
dc.contributor.authorBehrens, S
dc.contributor.authorBenitez, J
dc.contributor.authorBermisheva, M
dc.contributor.authorBernstein, L
dc.contributor.authorBlomqvist, C
dc.contributor.authorBoeckx, B
dc.contributor.authorBojesen, SE
dc.contributor.authorBonanni, B
dc.contributor.authorBørresen-Dale, A-L
dc.contributor.authorBrauch, H
dc.contributor.authorBrenner, H
dc.contributor.authorBrentnall, A
dc.contributor.authorBrinton, L
dc.contributor.authorBroberg, P
dc.contributor.authorBrock, IW
dc.contributor.authorBrucker, SY
dc.contributor.authorBurwinkel, B
dc.contributor.authorCaldas, C
dc.contributor.authorCaldés, T
dc.contributor.authorCampa, D
dc.contributor.authorCanzian, F
dc.contributor.authorCarracedo, A
dc.contributor.authorCarter, BD
dc.contributor.authorCastelao, JE
dc.contributor.authorChang-Claude, J
dc.contributor.authorChanock, SJ
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorCheng, T-YD
dc.contributor.authorChin, S-F
dc.contributor.authorClarke, CL
dc.contributor.authorNBCS Collaborators,
dc.contributor.authorCordina-Duverger, E
dc.contributor.authorCouch, FJ
dc.contributor.authorCox, DG
dc.contributor.authorCox, A
dc.contributor.authorCross, SS
dc.contributor.authorCzene, K
dc.contributor.authorDaly, MB
dc.contributor.authorDevilee, P
dc.contributor.authorDunn, JA
dc.contributor.authorDunning, AM
dc.contributor.authorDurcan, L
dc.contributor.authorDwek, M
dc.contributor.authorEarl, HM
dc.contributor.authorEkici, AB
dc.contributor.authorEliassen, AH
dc.contributor.authorEllberg, C
dc.contributor.authorEngel, C
dc.contributor.authorEriksson, M
dc.contributor.authorEvans, DG
dc.contributor.authorFigueroa, J
dc.contributor.authorFlesch-Janys, D
dc.contributor.authorFlyger, H
dc.contributor.authorGabrielson, M
dc.contributor.authorGago-Dominguez, M
dc.contributor.authorGalle, E
dc.contributor.authorGapstur, SM
dc.contributor.authorGarcía-Closas, M
dc.contributor.authorGarcía-Sáenz, JA
dc.contributor.authorGaudet, MM
dc.contributor.authorGeorge, A
dc.contributor.authorGeorgoulias, V
dc.contributor.authorGiles, GG
dc.contributor.authorGlendon, G
dc.contributor.authorGoldgar, DE
dc.contributor.authorGonzález-Neira, A
dc.contributor.authorAlnæs, GIG
dc.contributor.authorGrip, M
dc.contributor.authorGuénel, P
dc.contributor.authorHaeberle, L
dc.contributor.authorHahnen, E
dc.contributor.authorHaiman, CA
dc.contributor.authorHåkansson, N
dc.contributor.authorHall, P
dc.contributor.authorHamann, U
dc.contributor.authorHankinson, S
dc.contributor.authorHarkness, EF
dc.contributor.authorHarrington, PA
dc.contributor.authorHart, SN
dc.contributor.authorHartikainen, JM
dc.contributor.authorHein, A
dc.contributor.authorHillemanns, P
dc.contributor.authorHiller, L
dc.contributor.authorHolleczek, B
dc.contributor.authorHollestelle, A
dc.contributor.authorHooning, MJ
dc.contributor.authorHoover, RN
dc.contributor.authorHopper, JL
dc.contributor.authorHowell, A
dc.contributor.authorHuang, G
dc.contributor.authorHumphreys, K
dc.contributor.authorHunter, DJ
dc.contributor.authorJanni, W
dc.contributor.authorJohn, EM
dc.contributor.authorJones, ME
dc.contributor.authorJukkola-Vuorinen, A
dc.contributor.authorJung, A
dc.contributor.authorKaaks, R
dc.contributor.authorKabisch, M
dc.contributor.authorKaczmarek, K
dc.contributor.authorKerin, MJ
dc.contributor.authorKhan, S
dc.contributor.authorKhusnutdinova, E
dc.contributor.authorKiiski, JI
dc.contributor.authorKitahara, CM
dc.contributor.authorKnight, JA
dc.contributor.authorKo, Y-D
dc.contributor.authorKoppert, LB
dc.contributor.authorKosma, V-M
dc.contributor.authorKraft, P
dc.contributor.authorKristensen, VN
dc.contributor.authorKrüger, U
dc.contributor.authorKühl, T
dc.contributor.authorLambrechts, D
dc.contributor.authorLe Marchand, L
dc.contributor.authorLee, E
dc.contributor.authorLejbkowicz, F
dc.contributor.authorLi, L
dc.contributor.authorLindblom, A
dc.contributor.authorLindström, S
dc.contributor.authorLinet, M
dc.contributor.authorLissowska, J
dc.contributor.authorLo, W-Y
dc.contributor.authorLoibl, S
dc.contributor.authorLubiński, J
dc.contributor.authorLux, MP
dc.contributor.authorMacInnis, RJ
dc.contributor.authorMaierthaler, M
dc.contributor.authorMaishman, T
dc.contributor.authorMakalic, E
dc.contributor.authorMannermaa, A
dc.contributor.authorManoochehri, M
dc.contributor.authorManoukian, S
dc.contributor.authorMargolin, S
dc.contributor.authorMartinez, ME
dc.contributor.authorMavroudis, D
dc.contributor.authorMcLean, C
dc.contributor.authorMeindl, A
dc.contributor.authorMiddha, P
dc.contributor.authorMiller, N
dc.contributor.authorMilne, RL
dc.contributor.authorMoreno, F
dc.contributor.authorMulligan, AM
dc.contributor.authorMulot, C
dc.contributor.authorNassir, R
dc.contributor.authorNeuhausen, SL
dc.contributor.authorNewman, WT
dc.contributor.authorNielsen, SF
dc.contributor.authorNordestgaard, BG
dc.contributor.authorNorman, A
dc.contributor.authorOlsson, H
dc.contributor.authorOrr, N
dc.contributor.authorPankratz, VS
dc.contributor.authorPark-Simon, T-W
dc.contributor.authorPerez, JIA
dc.contributor.authorPérez-Barrios, C
dc.contributor.authorPeterlongo, P
dc.contributor.authorPetridis, C
dc.contributor.authorPinchev, M
dc.contributor.authorPrajzendanc, K
dc.contributor.authorPrentice, R
dc.contributor.authorPresneau, N
dc.contributor.authorProkofieva, D
dc.contributor.authorPylkäs, K
dc.contributor.authorRack, B
dc.contributor.authorRadice, P
dc.contributor.authorRamachandran, D
dc.contributor.authorRennert, G
dc.contributor.authorRennert, HS
dc.contributor.authorRhenius, V
dc.contributor.authorRomero, A
dc.contributor.authorRoylance, R
dc.contributor.authorSaloustros, E
dc.contributor.authorSawyer, EJ
dc.contributor.authorSchmidt, DF
dc.contributor.authorSchmutzler, RK
dc.contributor.authorSchneeweiss, A
dc.contributor.authorSchoemaker, MJ
dc.contributor.authorSchumacher, F
dc.contributor.authorSchwentner, L
dc.contributor.authorScott, RJ
dc.contributor.authorScott, C
dc.contributor.authorSeynaeve, C
dc.contributor.authorShah, M
dc.contributor.authorSimard, J
dc.contributor.authorSmeets, A
dc.contributor.authorSohn, C
dc.contributor.authorSouthey, MC
dc.contributor.authorSwerdlow, AJ
dc.contributor.authorTalhouk, A
dc.contributor.authorTamimi, RM
dc.contributor.authorTapper, WJ
dc.contributor.authorTeixeira, MR
dc.contributor.authorTengström, M
dc.contributor.authorTerry, MB
dc.contributor.authorThöne, K
dc.contributor.authorTollenaar, RAEM
dc.contributor.authorTomlinson, I
dc.contributor.authorTorres, D
dc.contributor.authorTruong, T
dc.contributor.authorTurman, C
dc.contributor.authorTurnbull, C
dc.contributor.authorUlmer, H-U
dc.contributor.authorUntch, M
dc.contributor.authorVachon, C
dc.contributor.authorvan Asperen, CJ
dc.contributor.authorvan den Ouweland, AMW
dc.contributor.authorvan Veen, EM
dc.contributor.authorWendt, C
dc.contributor.authorWhittemore, AS
dc.contributor.authorWillett, W
dc.contributor.authorWinqvist, R
dc.contributor.authorWolk, A
dc.contributor.authorYang, XR
dc.contributor.authorZhang, Y
dc.contributor.authorEaston, DF
dc.contributor.authorFasching, PA
dc.contributor.authorNevanlinna, H
dc.contributor.authorEccles, DM
dc.contributor.authorPharoah, PDP
dc.contributor.authorSchmidt, MK
dc.date.accessioned2019-03-11T12:09:12Z
dc.date.issued2019-03-19
dc.identifier.citationBritish journal of cancer, 2019, 120 (6), pp. 647 - 657
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3149
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-019-0393-x
dc.description.abstractBACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). RESULTS: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. CONCLUSIONS: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.
dc.formatPrint-Electronic
dc.format.extent647 - 657
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectNBCS Collaborators
dc.subjectChromosomes, Human, Pair 7
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectReceptors, Estrogen
dc.subjectPrognosis
dc.subjectProportional Hazards Models
dc.subjectBayes Theorem
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.titleGenome-wide association study of germline variants and breast cancer-specific mortality.
dc.typeJournal Article
dcterms.dateAccepted2019-01-14
rioxxterms.versionofrecord10.1038/s41416-019-0393-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue6
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.publication-statusPublished
pubs.volume120
pubs.embargo.termsNot known
icr.researchteamAetiological Epidemiology
dc.contributor.icrauthorJones, Michael
dc.contributor.icrauthorSchoemaker, Minouk
dc.contributor.icrauthorSwerdlow, Anthony
dc.contributor.icrauthorTurnbull, Clare


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